Balance between promiscuity and specificity in phage λ host range

Area of Science:

• Microbiology
• Evolutionary Biology
• Virology

Background:

• Viruses must overcome host resistance to survive, yet they maintain stable coevolutionary relationships with hosts.
• Understanding viral adaptation mechanisms is crucial for predicting pathogen evolution and managing infections.

Purpose of the Study:

• To investigate the molecular factors enabling bacteriophage lambda (λ) to adapt to resistant host strains of Escherichia coli.
• To map the fitness landscape of λ tail fiber tip protein mutations and identify adaptive pathways.

Main Methods:

• Deep mutational scanning of the λ tail fiber tip protein region responsible for host receptor binding.
• Selection experiments involving wild-type and resistant Escherichia coli strains with specific mutations in the λ receptor.
• Analysis of viral variants to distinguish between generalist (promiscuous) and specialist (host-specific) adaptation.

Main Results:

• The λ tail fiber tip protein exhibits a highly restrictive fitness landscape, with most mutations abolishing function.
• Specific mutation-tolerant positions in the tail fiber protein correlate with host range expansion.
• Selection on resistant hosts identified hundreds of adaptive λ variants, including those conferring promiscuous or host-specific infectivity.

Conclusions:

• Viral adaptation to resistant hosts is constrained by a restrictive fitness landscape but driven by specific tolerant sites.
• Both promiscuous and host-specific adaptive strategies contribute to viral success in overcoming host resistance.
• This study provides insights into the evolutionary mechanisms underlying virus-host coevolution and pathogen adaptation.